Ph.D.: Stanford University
Postdoctoral Training: University of California at Los Angeles
Honors: March of Dimes Basil O’Connor Scholar

Gene Regulation and Programmed Cell Death in Drosophila Development

Three fundamental aspects of metazoan development are pattern formation, cell differentiation, and cell death. The first two processes ensure that cells are specified correctly and acquire appropriate functional properties. The third permits the controlled elimination of cells which have failed in the first two, or that may have transient or deleterious functions. Our laboratory utilizes Drosophila as a model to study these processes. One focus is on functional analyses of a novel HMG box gene, fish-hook, which encodes a SOX protein related to SRY, the human testis determining factor. We have shown that fish is essential for proper segmentation, nervous system organization, and appendage formation. Fish DNA binding sites were identified in specific downstream target genes. The Fish protein has strong DNA bending and transcriptional activation properties. We are currently carrying out screens in yeast and flies to identify Fish-interacting proteins.

The second focus is on analyzing the regulation of programmed cell death. We are using the embryonic CNS midline cells to study the functions of several key Drosophila cell death activators. Our work has indicated that lineage specific midline cell death occurs, and is controlled by the combined functions of the related and linked reaper, head involution defective, and grim genes. Examination of mutations and use of the Gal4/UAS targeted gene expression system have revealed novel synergistic interactions between these genes, and identified gene-specific repression by cellular anti-apoptosis proteins. We are currently pursuing structure/function studies of these proteins and analyzing the functions of several other cell death regulators.

Representative publications:

Schreader, B.A. and Nambu, J.R. 2004. A fine balance for life and death decisions. Nature Structural and Molecular Biology , 11: 386-388.